ABSTRACT
Focused cardiac ultrasound (FoCUS) is becoming standard practice in a wide spectrum of clinical settings. There is limited data evaluating the real-world use of FoCUS with artificial intelligence (AI). Our objective was to determine the accuracy of FoCUS AI-assisted left ventricular ejection fraction (LVEF) assessment and compare its accuracy between novice and experienced users. In this prospective, multicentre study, participants requiring a transthoracic echocardiogram (TTE) were recruited to have a FoCUS done by a novice or experienced user. The AI-assisted device calculated LVEF at the bedside, which was subsequently compared to TTE. 449 participants were enrolled with 424 studies included in the final analysis. The overall intraclass coefficient was 0.904, and 0.921 in the novice (n = 208) and 0.845 in the experienced (n = 216) cohorts. There was a significant bias of 0.73% towards TTE (p = 0.005) with a level of agreement of 11.2%. Categorical grading of LVEF severity had excellent agreement to TTE (weighted kappa = 0.83). The area under the curve (AUC) was 0.98 for identifying an abnormal LVEF (<50%) with a sensitivity of 92.8%, specificity of 92.3%, negative predictive value (NPV) of 0.97 and a positive predictive value (PPV) of 0.83. In identifying severe dysfunction (<30%) the AUC was 0.99 with a sensitivity of 78.1%, specificity of 98.0%, NPV of 0.98 and PPV of 0.76. Here we report that FoCUS AI-assisted LVEF assessments provide highly reproducible LVEF estimations in comparison to formal TTE. This finding was consistent among senior and novice echocardiographers suggesting applicability in a variety of clinical settings.
ABSTRACT
INTRODUCTION: Signal peptide peptidase (SPP) is a GxGD-type intramembrane-cleaving aspartyl protease responsible for clearing accumulating signal peptides in the endoplasmic reticulum. SPP is conserved among all kingdoms and is essential for maintaining cell homeostasis. Inhibition of SPP with selective inhibitors and the structurally similar HIV protease inhibitors results in signal peptide accumulation and subsequent cell death. Identification of SPP homologues in major human parasitic infections has opened a new therapeutic opportunity. Moreover, the essentiality of mammalian SPP-mediated viral protein processing during infection is emerging. AREAS COVERED: This review introduces the discovery and biological function of human SPP enzymes and identify parasitic homologues as pharmacological targets of both SPP and HIV protease inhibitors. Later, the role of mammalian SPP during viral infection and how disruption of host SPP can be employed as a novel antiviral therapy are examined and discussed. EXPERT OPINION: Parasitic and viral infections cause severe health and economic burden, exacerbated by the lack of new therapeutics in the pipeline. SPP has been shown to be essential for malaria parasite growth and encouraging evidence in other parasites demonstrates broad essentiality of these proteases as therapeutic targets. As drug resistant parasite and viruses emerge, SPP inhibition will provide a new generation of compounds to counter the growing threat of antimicrobial resistance.
